Verapamil and tiapamil in prevention of ventricular fibrillation in pigs with coronary ligation. Comparative effects on left ventricular function

Abstract

Antiarrhythmic and hemodynamic effects of the calcium channel antagonist verapamil were compared with those of tiapamil, a congener, in open-chest pigs with anterior descending coronary artery ligation. Tiapamil (6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 4 of 10 versus 22 of 25 in controls (p < 0.05) and maintained left ventricular dP/dt(max) after ligation (predrug value: 2,312 ± 112 mm Hg/sec; 20 minutes after ligation: 2,139 ± 229 mm Hg/sec). Tiapamil increased blood flow in the peripheral ischemic zone (24 ± 3.2% vs. 16.9 ± 1.6% of preligation value in controls, p < 0.05) as well as in the peri-ischemic and nonischemic zones (153.9 ± 12.7% and 186.3 ± 17.1%, respectively; both p < 0.0001 vs. 97.9 ± 5% and 91.3 ± 4.7% in controls). Verapamil (0.6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 0 of 7 versus 22 of 25 in controls (p < 0.005); left ventricular dP/dt(max) decreased from 2,062 ± 144 to 1,060 ± 168 mm Hg/sec (p < 0.0001). Verapamil did not change blood flow in the peripheral, peri-ischemic, or nonischemic zones. Thus, tiapamil, and not verapamil, decreased ischemic ventricular fibrillation while maintaining left ventricular mechanical function. Verapamil congeners warrant further evaluation as antiarrhythmic agents in acute myocardial ischemia.